NMR metabolomics highlights sphingosine kinase-1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells
- Strong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase-1 (SK1) in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR- based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction in CO2 production. Additionally, SK1-expressing cells displayed a significant increase in glucose uptake paralleled by GLUT3 transporter upregulation. The role of SK1 is not limited to the induction of aerobic glycolysis, affecting metabolic pathways that appear to support theStrong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase-1 (SK1) in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR- based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction in CO2 production. Additionally, SK1-expressing cells displayed a significant increase in glucose uptake paralleled by GLUT3 transporter upregulation. The role of SK1 is not limited to the induction of aerobic glycolysis, affecting metabolic pathways that appear to support the biosynthesis of macromolecules. These findings highlight the role of SK1 signaling axis in cancer metabolic reprogramming, pointing out innovative strategies for cancer therapies.…
| Author details: | Caterina Bernacchioni, Veronica Ghini, Francesca Cencetti, Lukasz JaptokGND, Chiara Donati, Paola Bruni, Paola Turano |
|---|---|
| DOI: | https://doi.org/10.1002/1878-0261.12048 |
| ISSN: | 1878-0261 |
| Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/28258651 |
| Title of parent work (English): | Molecular oncology / Federation of European Biochemical Societies |
| Publisher: | Wiley |
| Place of publishing: | Hoboken |
| Publication type: | Article |
| Language: | English |
| Date of first publication: | 2017/03/04 |
| Publication year: | 2017 |
| Release date: | 2022/06/07 |
| Tag: | NMR-based metabolomics; Warburg effect; ovarian cancer; sphingosine kinase-1 |
| Volume: | 11 |
| Number of pages: | 17 |
| First page: | 517 |
| Last Page: | 533 |
| Funding institution: | Ente Cassa di Risparmio di Firenze [2014.0732, 2014.0162]; University of Florence (Fondi di Ateneo ex 60%) |
| Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
| DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
| Peer review: | Referiert |
| Publishing method: | Open Access / Gold Open-Access |
| DOAJ gelistet | |
| License (German): |  CC-BY - Namensnennung 4.0 International |
